The etiology of hypertension in obesity is unknown but may relate to nutrient activation of the sympathetic nervous system (SNS). The presence of noninsulin-dependent diabetes (NIDDM) in obesity may also alter BP control. Our premise is based on studies in animals and man that carbohydrate (CHO) ingestion activates SNS activity and that these responses may be accentuated in obesity. SNS activity will be compared in 4 study groups (N=15 each group) including obese hypertensives with and without NIDDM, and obese normotensives with and without NIDDM. The first phase of the protocol will evaluate patients on their normal outpatient diet examining basal plasma norepinephrine (NE) and vascular reactivity to infused NE. The effect ofan acute oral glucose load on BP, plasma NE and sodium excretion (UNa) will be compared in the four groups. The next phase of the study will be an inpatient evaluation of 7 days of low and high CHO diets on BP, SNS and vascular reactivity to NE. The role insulin in mediating CHO-induced activation of SNS and BP will also be examined. Insulin may have direct effects on BP by stimulating SNS and suppressing UNa. Fasting and 60 min postprandial insulin levels will be correlated with BP in the 4 study groups. Using the euglycemic clamp, insulin will be infused in obese subjects with measurement of plasma NE, BP and UNa every 30 min for 120 min. In separate euglycemic clamp studies, vascular reactivity to NE will be examined during induced hyperinsulinemia to evaluate if insulin enhances vascular reactivity. Finally, the combined effect of 7 days high CHO-high sodium diet on BP, NE and vascular reactivity will be studied. These studies should delineate if the hyper-insulinemia of obesity contributes to enhanced activation of SNS in obese hypertensive subjects. By examining the 4 study groups the separate effect of hyperglycemia on BP and hormonal systems can be compared to delineate what components of high BP are related to obesity versus that due to other metabolic abnormalities of NIDDM. Detection of SNS hyperactivity in obese hypertensive patients would allow more specific therapy through dietary reduction in CHO to reduce BP.